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Human Glucagon Expression Is under the Control of miR-320a.
Citation | “Human Glucagon Expression Is Under The Control Of Mir-320A.”. Endocrinology. . |
Center | University of Alabama at Birmingham |
Author | SeongHo Jo, Guanlan Xu, Gu Jing, Junqin Chen, Anath Shalev |
Keywords | alpha cells, diabetes, glucagon, human islets, microRNA |
Abstract |
Increased glucagon is a hallmark of diabetes and leads to worsening of the hyperglycemia, but the molecular mechanisms causing it are still unknown. We therefore investigated the possibility that microRNAs might be involved in the regulation of glucagon. Indeed, analysis of the glucagon 3' untranslated region (UTR) revealed potential binding sites for miR-320a, and using luciferase reporter assays we found that miR-320a directly targets the 3' UTRs of human and rodent glucagon. In addition, endogenous glucagon mRNA and protein expression as well as glucagon secretion were reduced in response to miR-320a overexpression, whereas inhibition of miR-320a upregulated glucagon expression. Interestingly, miR-320a expression was decreased by high glucose, and this was associated with an increase in glucagon expression in human islets and mouse αTC1-6 cells. Moreover, miR-320a overexpression completely blunted these effects. Importantly, miR-320a was also significantly downregulated in human islets of subjects with type 2 diabetes and this was accompanied by increased glucagon expression. Thus, our data suggest that glucose-induced downregulation of miR-320a may contribute to the paradoxical increase in glucagon observed in type 2 diabetes and reveal for the first time that glucagon expression is under the control by a microRNA providing novel insight into the abnormal regulation of glucagon in diabetes. |
Year of Publication |
2021
|
Journal |
Endocrinology
|
Volume |
162
|
Issue |
3
|
Date Published |
03/2021
|
ISSN Number |
1945-7170
|
DOI |
10.1210/endocr/bqaa238
|
Alternate Journal |
Endocrinology
|
PMID |
33367814
|
PMCID |
PMC7814302
|
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